The immune mechanism(s) by which humans or experimental animals acquire resistance to Lyme disease is poorly understood. We found that mature immunocompetent LSH/Ss hamsters infected with Borrelia burgdorferi develop carditis, inflammation of the central nervous system and arthritis. The arthritis resembles the histopathologic response of Lyme arthritis in humans. When hamsters are exposed to radiation and infected with B. burgdorferi the arthritis is exacerbated. Swelling of the hind paws consistently occurs within 8 days after infection with the Lyme disease spirochete. In addition, two other parameters can be measured: histopathologic response of the hind joints and recovery of B. burgdorferi from tissues. These highly reproducible responses (100%) in irradiated hamsters are used to monitor the humoral and cellular immune mechanisms of mature immunocompetent hamsters infected with B. burgdorferi by passive transfer of immunity studies. The specific aims of this proposal are to determine: 1) the kinetics of the protective antibody response and its relationship to reinfection, 2) whether protection against the Lyme disease spirochete can be conferred on recipient hamsters with components of immune serum (IgGl, IgG2 or IgM), 3) the role of complement, 4) an in vitro corollary of in vivo passive protection and whether cross-protection develops among isolates of B. burgdorferi and 5) the role of normal and immune cells (T and B, B, T, and T subsets) in conferring protection on recipient hamsters against challenge with B. burgdorferi. This proposal is investigating the effects of vaccination with an infectious isolate of B. burgdorferi. No vaccine (non-infectious) is going to be licensed for use in humans without understanding the host-parasite responses. Investigations of the mechanisms of resistance in hamsters challenged with B. burgdorferi will delineate mechanisms by which humans respond to infection or vaccination.